Throughout this application, various publications are referenced. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications are hereby incorporated by reference into this application to describe more fully the art to which this invention pertains.
The human glycoprotein gonadotropic hormones: luteinizing hormone (hLH), follicle stimulating hormone (hFSH), and chorionic gonadotropin (hCG), are essential for reproduction. These hormones, along with thyroid stimulating hormone (hTSH), are composed of a common xcex1 subunit noncovalently combined with a target-specific xcex2 subunit (Pierce and Parsons, 1981; Hussa, 1987). They appear in blood and urine in a variety of forms ranging from the heterodimeric intact molecules to small fragments (Pierce and Parsons, 1981; Hussa, 1987). All of the glycoprotein hormones are produced by the pituitary, including a small quantity of human chorionic gonadotropin (Hartree et al., 1983), which is primarily a placental product and is excreted in high concentration in first trimester pregnancy urine.
This invention further provides a method for detecting the presence of human malignant cells in a sample of tumor cells, which comprises contacting the sample with an antibody directed to an epitope present on (i) the xcex2 subunit of human luteinizing hormone, (ii) the xcex2 subunit of human chorionic gonadotropin, (iii) intact human luteinizing hormone, or (iv) intact human chorionic gonadotropin, under conditions such that the antibody forms a complex with cells present in the sample if the epitope is present on the surface of the cells, and determining whether the antibody forms such a complex so as to thereby detect the presence of human malignant cells in the sample.
This invention further provides a method for determining whether a tumor present in a human subject is malignant which comprises obtaining a sample of cells from the tumor and detecting the presence of malignant cells in the sample according to the method of the subject invention so as to thereby determine whether the tumor is malignant.
This invention further provides a method for obtaining an enriched population of live human malignant cells which comprises contacting a population of cells comprising live human malignant cells with an antibody directed to an epitope present on (i) the xcex2 subunit of human luteinizing hormone, (ii) the xcex2 subunit of human chorionic gonadotropin, (iii) intact human luteinizing hormone, or (iv) intact human chorionic gonadotropin, under conditions such that the antibody forms a complex with the cells present in the population if the epitope is present on the surface of the cells, and isolating the cells which form a complex with the antibody so as to obtain an enriched population of live human malignant cells.
This invention further provides a method for determining the amount of intact luteinizing hormone in a sample which comprises contacting the sample with a suitable amount of antibody directed to an epitope present only on intact luteinizing hormone under conditions permitting the formation of a complex between the antibody and the epitope, determining the amount of complex so formed, and comparing the amount of complex so formed to a known standard so as to thereby determine the amount of intact luteinizing hormone in the sample.
This invention further provides a method for determining the ovulatory stage of a subject which comprises obtaining a suitable sample from the subject, determining the amount of intact luteinizing hormone in the sample according to the method of the subject invention, and comparing the amount of intact luteinizing hormone so determined to a known standard so as to determine the ovulatory stage of the subject.
This invention further provides a method for determining the amount of intact follicle stimulating hormone in a sample which comprises contacting the sample with a suitable amount of antibody directed to an epitope present on intact follicle stimulating hormone under conditions permitting the formation of a complex between the antibody and the epitope, determining the amount of complex so formed, and comparing the amount of complex so formed to a known standard so as to thereby determine the amount of intact follicle stimulating hormone in the sample.
This invention further provides a method for determining the ovulatory stage of a subject which comprises obtaining a suitable sample from the subject, determining the amount of intact follicle stimulating hormone in the sample according to the method of the subject invention, and comparing the amount of intact follicle stimulating hormone so determined to the amount of intact follicle stimulating hormone present in a sample from a subject at a known ovulatory stage so as to determine the ovulatory stage of the subject.
This invention further provides a method for determining the amount of intact human chorionic gonadotropin in a sample which comprises contacting the sample with a suitable amount of antibody directed to an epitope present only on intact human chorionic gonadotropin under conditions permitting the formation of a complex between the antibody and the epitope, determining the amount of complex so formed, and comparing the amount of complex so formed to a known standard so as to thereby determine the amount of intact human chorionic gonadotropin in the sample.
This invention further provides a method for determining whether a subject is pregnant which comprises obtaining a suitable sample from the subject, determining the amount of intact human chorionic gonadotropin in the sample according to the method of the subject invention, and comparing the amount of intact human chorionic gonadotropin so determined to a known standard so as to determine whether the subject is pregnant.
This invention further provides a method for determining the ovulatory stage of a subject which comprises obtaining a suitable sample from the subject, determining the amount of intact human chorionic gonadotropin in the sample according to the method of the subject invention, and comparing the amount of intact human chorionic gonadotropin so determined to the amount of intact human chorionic gonadotropin present in a sample from a subject at a known ovulatory stage so as to determine the ovulatory stage of the subject.
This invention further provides a method for determining the amount of free xcex1 subunit of human luteinizing hormone in a sample which comprises contacting the sample with a suitable amount of antibody directed to an epitope present on the a subunit of human luteinizing hormone under conditions permitting the formation of a complex between the antibody and the epitope, determining the amount of complex so formed, and comparing the amount of complex so formed to a known standard so as to thereby determine the amount of free xcex1 subunit of human luteinizing hormone in the sample.
This invention further provides a method for determining whether a subject has a malignant tumor which comprises obtaining a suitable sample from the subject, determining the amount of free xcex1 subunit of human luteinizing hormone in the sample according to the method of the subject invention, and comparing the amount of free xcex1 subunit of human luteinizing hormone so determined to a known standard so as to determine whether the subject has a malignant tumor.
This invention further provides a method for determining the amount of nicked human chorionic gonadotropin in a sample which comprises contacting the sample with a suitable amount of antibody which preferentially binds to an epitope present only on nicked human chorionic gonadotropin under conditions permitting the formation of a complex between the antibody and the epitope, determining the amount of complex so formed, and comparing the amount of complex so formed to a known standard so as to thereby determine the amount of nicked human chorionic gonadotropin in the sample.
This invention further provides a method for determining whether a subject is pregnant which comprises obtaining a suitable sample from the subject, determining the amount of nicked human chorionic gonadotropin in the sample according to the method of the subject invention, and comparing the amount of nicked human chorionic gonadotropin so determined to an amount of nicked human chorionic gonadotropin correlative with a known state of pregnancy so as to determine whether the subject is pregnant. In the preferred embodiment, the suitable sample is a urine sample.
This invention further provides a method for determining whether a subject has a malignant tumor which comprises obtaining a suitable sample from the subject, determining the amount of nicked human chorionic gonadotropin in the sample according to the method of the subject invention, and comparing the amount of nicked human chorionic gonadotropin so determined to a known standard so as to determine whether the subject has a malignant tumor. In the preferred embodiment, the suitable sample is a urine sample.
Finally, this invention provides a method for determining the likelihood of a fetus""s being afflicted with Down""s syndrome which comprises obtaining a suitable sample from the mother of the fetus, determining the ratio of the amount of free human chorionic gonadotropin xcex2 subunit in the sample to the amount of intact human chorionic gonadotropin in the sample, and comparing the ratio so determined to a known standard so as to determine the likelihood of the fetus""s being afflicted with Down""s syndrome.